Exp Mol Med.
2008 Oct;40(5):514-522. 10.3858/emm.2008.40.5.514.
LYR71, a derivative of trimeric resveratrol, inhibits tumorigenesis by blocking STAT3-mediated matrix metalloproteinase 9 expression
- Affiliations
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- 1Department of Pharmacology, Seoul National University College of Medicine, Seoul, Korea. sangkyu@snu.ac.kr
- 2Department of Anatomy, Seoul National University College of Medicine, Seoul, Korea.
- 3Cancer Research Institute, Department of Tumor Biology, Seoul National University College of Medicine, Seoul, Korea.
- 4College of Pharmacy and Research Center for, Bioresource and Health, Chungbuk National University, Cheongju, Korea.
- KMID: 1104805
- DOI: http://doi.org/10.3858/emm.2008.40.5.514
Abstract
- Tumor migration/invasion is the main cause of tumor progression and STAT3 is needed to enhance tumor migration/invasion by up-regulating MMP-9. Thus, agents that inhibit STAT3 activation may be used as an anticancer drug. We present herein that 6-methyl-2-propylimino-6, 7-dihydro-5H-benzo [1, 3]-oxathiol- 4-one (LYR71) , a derivative of trimeric resveratrol, has an anticancer activity through inhibition of STAT3 activation. We found that LYR71 suppressed STAT3 activation and inhibited the expression and activity of MMP-9 in RANTES-stimulated breast cancer cells. In addition, LYR71 reduced RANTES-induced MMP-9 transcripts by blocking STAT3 recruitment, dissociating p300 and deacetylating histone H3 and H4 on the MMP-9 promoter. Furthermore, LYR71 inhibited tumor migration/invasion in RANTES-treated breast cancer cells and consequently blocked tumor progression in tumor-bearing mice. Taken together, the results of this study suggest that LYR71 can be therapeutically useful due to the inhibition effect of STAT3-mediated MMP-9 expression in breast cancer cells.
Keyword
MeSH Terms
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Animals
Antineoplastic Agents/chemistry/*pharmacology
Bicyclo Compounds, Heterocyclic/chemistry/*pharmacology
Blotting, Western
Breast Neoplasms/genetics/metabolism/pathology
Cell Line, Tumor
Cell Movement/drug effects
Cell Survival/drug effects
Chromatin Immunoprecipitation
Female
Gene Expression/drug effects
Humans
Imines/chemistry/*pharmacology
Immunohistochemistry
Mammary Neoplasms, Experimental/pathology/prevention & control
Matrix Metalloproteinase 9/genetics/*metabolism
Mice
Mice, Inbred BALB C
Mice, Nude
Molecular Structure
Phosphorylation/drug effects
Reverse Transcriptase Polymerase Chain Reaction
STAT3 Transcription Factor/genetics/*metabolism
Stilbenes/chemistry
Xenograft Model Antitumor Assays/methods
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